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Hydrogenolysis. Reagents and conditions: (a) H2, Pd/C, EtOAc, rt, 24 h, 99% (56), 98% (57), 50% (58), 45% (59).
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Microbial ipso,ortho-dihydroxylation of benzoic acid by the B9 mutant strain of Ralstonia eutropha permits rapid construction of aminocyclitols containing a quaternary stereocentre. Installation of the amine functionality is achieved by use of an acylnitroso dienophile for a hetero-Diels–Alder reaction. Both aminotetrols and aminohexols are accessi...
Citations
... The synthesis of aminocyclitols has attracted attention because they contain substructures of many biologically active natural products [1][2][3]. They have become important structural components for drug development with a modifying action as inhibitors of glycosidases [4][5][6][7][8][9][10]. Aminocyclitols are amino polyhydroxy cycloalkanes [2] formally derived from cyclitols [11][12][13][14][15], which are polyhydroxylated cycloalkanes, via replacement of one of the hydroxy groups with an amino group. ...
The efficient synthesis of two new stereoisomeric 3-aminocyclooctanetriols and their new halocyclitol derivatives starting from cis,cis -1,3-cyclooctadiene are reported. Reduction of cyclooctene endoperoxide, obtained by photooxygenation of cis,cis -1,3-cyclooctadiene, with zinc yielded a cyclooctene diol followed by acetylation of the hydroxy group, which gave dioldiacetate by OsO 4 /NMO oxidation. The cyclooctane dioldiacetate prepared was converted to the corresponding cyclic sulfate via the formation of a cyclic sulfite in the presence of catalytic RuO 4 . The reaction of this cyclic sulfate with a nucleophilic azide followed by the reduction of the azide group provided the target, 3-aminocyclooctanetriol. The second key compound, bromotriol, was prepared by epoxidation of the cyclooctenediol with m -chloroperbenzoic acid followed by hydrolysis with HBr(g) in methanol. Treatment of bromotriol with NaN 3 and the reduction of the azide group yielded the other desired 3-aminocyclooctanetriol. Hydrolysis of the epoxides with HCl(g) in methanol gave stereospecifically new chlorocyclooctanetriols.
... [199][200][201][202][203][204] Dihydroxylation of the alkene component of 3,6-dihydro-2H-1,2-oxazines is frequently employed method for functionalization of these compounds (e.g., as synthetic intermediates the synthesis of various amino-sugar derivatives). Most commonly, osmium tetroxide is used as the dihydroxylating agent 18,51,73,74,89,[205][206][207][208][209][210] but potassium osmate has also been used successfully. 177,211 Fig. 18 shows several examples of dihydroxylation products 134-138 in which no other functional groups besides the alkene were affected. ...
... Consequently, NdO cleavage is the most frequent type of reaction performed on such compounds. Most commonly, hydrogenolysis of the NdO bond occurs at approximately one atmosphere of hydrogen pressure and with transition metal catalysts such as Pd/C 7,18,49,53,57,60,72,75,89,105,161,169,177,182,194,206,210,222,[225][226][227]234,[341][342][343][344][345][346][347] or Raney Ni. 39,59,151,178,208,315,316,[319][320][321][322][323][324][325]329,348 The direct hydrogenolysis products of various 1,2-oxazinanes 328-335 are shown in Fig. 23. In all examples shown, no other functional group was affected in the transformation except for the direct hydrogenation of the NdO bond. ...
... While these hydrogenation conditions effectively cleave most NdO bonds of 1,2-oxazinanes to their corresponding amino alcohols, other functional groups that are sensitive to hydrogenation are usually also reduced (e.g., alkenes, azides, halogens, or O-and N-benzyl groups). 18,49,75,89,105,206,222,[225][226][227]321,324,342,344,347,348 Additionally, further reactivity may be initiated by the resulting amine or alcohol groups, such as condensations, nucleophilic substitutions, amidations, and/or esterifications (discussed below). ...
Developments in the chemistry of 1,2-oxazines and their benzo derivatives from 2007 to 2018 have been reviewed. Emphasis has been placed on describing numerous advances made in the reactivity and synthesis of 1,2-oxazines. In addition, structural characterization, theoretical analysis, thermodynamics, and applications of 1,2-oxazines within the review period are noted.
... The densely-packed, diverse functionality in these chirons finds ready application in different areas such as synthesis of natural products, 4 pharmaceuticals, 5 carbohydrates, 6 polymers 7 and dyes. 8 To date, in excess of 400 arene cis-diol products have been reported. ...
... The resulting oil was purified via flash column chromatography (60 : 35 : 2.5 : 2.5 EtOAc-petrol-H 2 O-AcOH) to yield pure 5 (625 mg, 71%) as a white crystalline solid. m.pt = 112-115°C; Synthesis of methyl (1S,2R)-1,2-dihydroxycyclohexane-1-carboxylate (6). To a stirred solution of 5 (47 mg, 0.29 mmol) dissolved in MeOH-C 6 H 6 (6 mL, 1 : 1), was added dropwise TMS-CHN 2 (0.200 mL, 2.0 M solution in THF, 0.400 mmol, 1.4 equiv.) ...
... The solution was filtered through MgSO 4 and concentrated under reduced pressure. The resulting oil was purified via flash column chromatography (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) to give 23 (45 mg, 13%) as a colourless oil and 24 (19 mg, 5%) as a colourless oil. ...
Oxidation of benzoic acid by a microorganism expressing benzoate dioxygenase leads to the formation of an unusual ipso, ortho arene cis-diol in sufficient quantities to be useful for synthesis. This homochiral diol possesses an array of differentiated functionality which can be exploited to access diverse highly oxygenated structures by concise synthetic sequences.
... The chemistry outlined in Scheme 17 was also applied to formal syntheses of oseltamivir 33 and gabaculine. 34 In 2013 we revisited the inosaminoacid chemistry we had described two years previously, this time targeting structures bearing a side chain in a lower oxidation state; 35 these were anticipated to have differing solubilities to the zwitterionic inosaminoacids 107-108 shown in Scheme 13. The chemistry bears many similarities to the previous report, but one notable difference is the reversal in regioselectivity for the acylnitroso cycloaddition when the side chain is in a lower oxidation state (Scheme 18). ...
The dearomatising dihydroxylation of aromatic molecules mediated by arene dioxygenase enzymes can provide cyclohexadiene-diols that are versatile starting materials for organic synthesis. Whereas oxidation of a substituted arene to give its ortho,meta-dihydrodiol has been demonstrated for numerous substrates and dioxygenases, formation of ipso,ortho-dihydrodiols has historically been underutilised in comparison. This feature article presents a chronological account of reported uses of such diols.
The synthesis of new bicyclic lactone derivatives was carried out starting from 2-methyl/phenyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione. 6-(Hydroxymethyl)-N-methyl/phenylcyclohex-3-ene-1-carboxamide derivatives were obtained from the reduction of tetrahydro-1H-isoindole-1,3(2H)-diones with NaBH4. Bromination and epoxidation reactions of both compounds were examined, and the structures of the resulting products were determined by spectroscopic methods. Substituted bicyclic lactone compounds, which are interesting rearrangement products in both bromination and epoxidation reactions, were obtained. In particular, hydroxymethyl (−CH2OH) and amide (−CONHR) groups attached to the cyclohexene ring in the bromination and epoxidation reactions were found to be effective in product formation. As a result, a new and applicable method was developed for the synthesis of bicyclic lactone derivatives.
Concise synthesis of ent-conduramine C-1 and its derivatives has been achieved by using commercially available d-ribose. The key steps in the synthesis are regioselective and diastereoselective amination of polybenzyl ethers by chlorosulfonyl isocyanate (CSI), chelation-controlled carbonyl addition, and intramolecular olefin metathesis. All of the synthesized compounds were evaluated for inhibitory activity against α-glucosidase. The derivatives 18 (IC50 = 0.65 ± 0.03 mM) and 19 (IC50 = 0.26 ± 0.01 mM) were identified to be more potent than well-known α-glucosidase inhibitor acarbose (IC50 = 1.05 ± 0.17 mM) as a positive control.
The chemoenzymatic dihydroxylation of arenes by microbial organisms represents a unique reaction found in nature. The reaction is highly stereo-, regio-, and enantioselective and yields versatile metabolites that have been exploited in the synthesis of countless natural products and useful homochiral building blocks. This chapter provides a brief history of the discovery and development of the microbial diol metabolites, their synthetic utility, and evolving applications in total synthesis. An extensive table is included to depict the many natural products and related synthetic targets attained through syntheses starting from cis-dihydrocatechols. The authors hope to highlight the utility of these chiral synthons in the assembly of natural products and to demonstrate the importance of incorporating biological methods into enantioselective synthesis.
2-Azidocyclooct-3-en-1-ol was used as a key compound for the synthesis of various eight-membered ring aminocyclitols. The double bond was subjected to an epoxidation reaction for further functionalization. The azidoepoxide obtained was subjected to a ring-opening reaction with HCl(g) in methanol. 2-Amino-4-chlorocyclooctanediol was synthesized as a single isomer in high yield. Benzylation of the hydroxyl group in 2-azidocyclooct-3-en-1-ol followed by an epoxidation reaction, acetolysis of the epoxide ring, and benzyl deprotection resulted in the unexpected formation of two azido-cyclooctanetriol isomers. Subsequently, hydrogenation of the azide group in these isomers afforded 3-amino- and 2-aminocyclooctanetriols. The mechanism of the formation of the products is discussed. Epoxidation of cyclooctene endoperoxide, which was the second key compound, followed by hydrogenation and azidolysis of epoxy-diol provided the target 3-aminocyclooctanetriol as the sole product.
cis-1,2-dihydrocatechols 5 (X= Me and Cl), which are available in homochiral form through the whole-cell biotransformation of toluene and chlorobenzene, respectively, undergo Diels-Alder cycloaddition reactions with certain electron-deficient dienophiles at 19 kbar (1.9 GPa). The favored products of such reactions are adducts of the general form 8 and that arise through the operation of a contrasteric or syn-addition pathway. In contrast, the acetonide derivatives, 9, of metabolites 5 undergo anti-selective addition reactions under the same conditions and so producing adducts of the general form 10. Bicyclo[2.2.2]octenes 8 and 10, which embody carbocyclic frameworks of opposite enantiomeric form, are useful scaffolds for chemical synthesis. Computational studies reveal that syn-adduct formation is thermodynamically favored over anti-adduct formation when the free diols 5 are involved but the reverse is so when the corresponding acetonides participate as the 4π-addend. Furthermore, the reactions become more exothermic as pressure increases while, concurrently, the activation barrier diminishes and at 6 GPa (60 kbar) almost vanishes.
A short synthetic route to a small library of aminocyclitols 14·HCl-19·HCl has been elaborated from the common shikimic acid-derived scaffolds 20 and 21. The developed strategy features three oxidative processes ‒ ozonolysis, dihydroxylation and epoxidation ‒ as the key transformations. The stereochemistry of the newly created stereocentres was confirmed either via crystallographic analysis or by means of NOESY experiments conducted on advanced intermediates. Glycosidase inhibition study revealed no glucosidase inhibition and only weak inhibitory activity against recombinant Drosophila melanogaster Golgi mannosidase (GMIIb).
